Similarity between cutaneous reactions due to SARS-CoV-2 and its vaccinations

the common


Morbiliform eruptions
Maculopapular rash, which also includes morbilliform eruptions, is the most common cutaneous side effect of the COVID-19 followed by CLL. The morbilliform eruption is also one of the common side effects of the COVID-19 vaccines and usually has a mild course [1,2]. Considering the characteristic formation and disappearance times of CLL lesions, there is also no significant difference between the lesions that occurred after the COVID-19 and SARS-CoV-2 vaccination.

Pityriasis rosea & urticaria
We previously reported that there is an increased number of urticaria and pityriasis rosea (PR) during the COVID-19 pandemic when compared with the corresponding previous year of the current pandemic. Subsequent reports suggested that patients with COVID-19 who have PR-like dermatosis and urticarial rash include SARS-CoV-2 particles in their skin lesions [8]. Similarly, numerous cases contain reports that PR-like dermatitis and urticaria can be developed after COVID-19 vaccines. Of note, in our daily routine practice, we also encountered numerous cases of new urticarial eruptions after both inactivated and mRNA-based COVID-19 vaccines. As per our observations PR cases that developed after SARS-CoV-2 vaccinations were not demographically distinct from the ordinary and general PR. Interestingly, there is a higher incidence of PR cases among inactivated SARS-CoV-2 vaccines in the literature [1]. The exact effect of the differences should be illuminated with further studies.

Herpes zoster
Herpes zoster can be triggered by COVID-19 vaccines. The occurrence of herpes zoster after the COVID-19 vaccine is mostly within 7-10 days. Interestingly, there is a report that even though a patient who has been vaccinated against the herpes zoster virus developed herpes zoster after COVID-19 vaccination. Similarly, to date, there are over 30 reports which suggested the possible relationship between COVID-19 and herpes zoster. The majority of cases of herpes zoster in patients with COVID-19 have a typical clinical presentation [9]. Considering the characteristic formation and disappearance times of herpes zoster lesions reveals similarity between cutaneous reactions due to SARS-CoV-2 and its vaccinations.

Erythema multiforme
Many types of drug reactions including erythema multiforme, which developed after COVID-19, have been reported. Similarly, four cases of mRNA vaccine-related erythema multiforme have been recently documented [1,2]. Increased vaccine-mediated immune boosting may lead to delayed hypersensitivity reaction which is responsible for erythema multiforme like reactions.

Other cutaneous manifestations
Apart from relatively common similar cutaneous manifestations of COVID-19 and its vaccine aforementioned above, there are certain rare skin disorders that can be seen as a result of both COVID-19 and its vaccine. These disorders can be listed as vesiculobullous eruptions, lichen planus, granuloma annulare, erythema annulare centrifugum, flare of herpes simplex, Rowell's syndrome, DRESS syndrome, and recurrence of alopecia areata. Of note, to date, there are still no reports on the relationship between livedo reticularis-like eruption, one of the main serious cutaneous manifestations of the COVID-19 and COVID-19 vaccines.
In the early stages of the pandemic, cutaneous side effects of SARS-CoV-2 were described, while in the current stages of the pandemic, cutaneous side effects of the COVID-19 vaccine were described. In general, these cutaneous side effects are commonly temporary, benign, self-limited and generally not a contraindication to further doses of the vaccine. In this article, we would like researchers to pay attention to the similarity between cutaneous reactions due to SARS-CoV-2 and its vaccinations.

Future perspective
The immune-based skin reactions due to both conditions may show that SARS-CoV-2 has a more immunological effect rather than infectious effect on the skin as in toxic shock syndrome. In addition, mRNA containing lipid nanoparticles found in COVID-19 vaccines can trigger autoimmunity by increasing the production of proinflammatory cytokines and chemokines. Furthermore, we know that the vaccines have mostly been developed against the antigenic Spike protein of the SARS-CoV-2 virus. Therefore, we would like to emphasize that the Skin manifestations associated with COVID-19 apart from livedo reticularis-like eruption are usually associated with milder disease, while it is not yet known whether the presence of post-vaccination skin findings is a strong or weak indicator of vaccine immunity. This condition is another gap that should be filled. As a result, further novel studies are required in order to find the exact pathogenesis of the cutaneous manifestations of SARS-CoV-2. In this context, addressing COVID-19 and its vaccine together may lead to new discoveries on the disease.
In the meantime, air pollution may increase the risk of getting coronavirus. Recent research from Rachel Nethery, Xiauo Wu, Francesca Dominici and other colleagues at Harvard showed that people who live in places with poor air quality are more likely to die from COVID-19 despite other factors such as pre-existing medical conditions, socioeconomic status and access to healthcare [10]. The comparison of cutaneous manifestations of vaccinations between the different air pollution areas may give certain indirect clues regarding the effects of COVID-19 and vaccines. In the next future, the effect of the different environmental conditions on the virus and vaccines may be important fields to deal with.

Author contributions
O Kutlu did the manuscript conception.Ö Kutlu and SA Temiz fulfilled the following contributions to the article: substantial contributions to the conception or design; or the acquisition, analysis or interpretation of data; drafting or revising critically for important intellectual content; final approval of the version to be published; agreement to be accountable for all aspects, ensuring that questions related to the accuracy or integrity of any part are appropriately investigated and resolved.

Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.